Interleukin-10 functions in vitro and in vivo to inhibit bacterial DNA-induced secretion of interleukin-12.
Bacterial DNA (bDNA) has a number of biologic properties, including the ability to induce interleukin-12 (IL-12) production by macrophages. We studied the role of the regulatory cytokine IL-10 as a potential inhibitor of bDNA-induced IL-12 production. IL-10 concentrations as low as 0.3 ng/ml profoundly inhibited bDNA-induced macrophage IL-12 production as measured by Elispot analysis of IL-12 p40-secreting cells. Additionally, we found that IL-10 inhibited bDNA-induced IL-12 secretion by the macrophage cell lines J774 and RAW 264. Preincubation of splenic adherent cells with IL-10 markedly reduced bDNA-induced transcription of IL-12 p40 mRNA. Interestingly, after 2 h of exposure, bDNA also induces transcription of IL-10 mRNA by splenic adherent cells. The importance of IL-10 in the in vivo regulation of bDNA-induced cytokine secretion was illustrated by the response of mice with disrupted IL-10 genes (IL-10 ko mice) to i.v. bDNA challenge. Compared to +/+ mice, IL-10 knockout (ko) mice exhibited increased numbers of IL-12 and interferon-gamma (IFN-gamma)-secreting cells following either single or repeated challenge with bDNA. These findings indicate that IL-10 plays a key role in regulating bDNA-induced production of inflammatory cytokines.
Anitescu
M
M
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242-1009, USA.
Chace
J H
JH
Tuetken
R
R
Yi
A K
AK
Berg
D J
DJ
Krieg
A M
AM
Cowdery
J S
JS
D000818:Animals; D002460:Cell Line; D004269:DNA, Bacterial / Q000235:genetics*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000502:physiology*; D018664:Interleukin-12 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D012636:Secretory Rate / Q000187:drug effects
D004269:DNA, Bacterial; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma